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Mohammad Abu Zaid, Paul C. Dinh Jr, Patrick O. Monahan, Chunkit Fung, Omar El-Charif, Darren R. Feldman, Robert J. Hamilton, David J. Vaughn, Clair J. Beard, Ryan Cook, Sandra Althouse, Shirin Ardeshir-Rouhani-Fard, Howard D. Sesso, Robert Huddart, Taisei Mushiroda, Michiaki Kubo, M. Eileen Dolan, Lawrence H. Einhorn, Sophie D. Fossa, Lois B. Travis and for the Platinum Study Group

Background: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. Patients and Methods: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone–binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. Results: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7–68.4 years), 38.5% had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P= .006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P= .011) or ≥30 kg/m2 (OR, 2.36; P= .005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P= .09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P= .07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65% vs 51%; P= .003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P<.001) or hypertension (18.5% vs 10.6%; P= .013), and to report erectile dysfunction (19.6% vs 11.9%; P= .018) or peripheral neuropathy (30.7% vs 22.5%; P= .041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P= .07) or anxiety/depression (14.8% vs 9.3%; P= .06) was observed. Conclusions: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients.

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Jarushka Naidoo

Immunotherapy is now the fourth pillar of cancer treatment, but the methodology used to determine who will benefit is still a work in progress. PD-L1 is commonly used as a predictive biomarker for immunotherapy, but others—such as immunogenic tumor biomarkers, host environment biomarkers and biomarkers of nonresponse—are being actively investigated. Additionally, research in combining biomarkers is currently being conducted, with new data emerging all the time.

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Aysegul A. Sahin, Timothy D. Gilligan and Jimmy J. Caudell

Three experts discussed changes in the 8th edition of the AJCC Cancer Staging Manual and challenges regarding these changes for staging of breast cancer, testicular cancer, and head and neck cancer, respectively. In general, the staging changes for breast cancer and for human papillomavirus–positive oropharyngeal cancer were hailed as improvements, but the changes for testicular cancer were questioned as to their clinical relevance. Better studies are needed to improve staging for human papillomavirus–negative oropharyngeal cancer.

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Stephen J. Bagley, Suzanna Talento, Nandita Mitra, Neal J. Meropol, Roger B. Cohen, Corey J. Langer and Anil Vachani

Background: Despite recent advances in targeted therapy and immunotherapy for advanced non–small cell lung cancer (NSCLC), carboplatin/pemetrexed/bevacizumab remains a commonly used first-line regimen. However, it is unknown whether the addition of bevacizumab to carboplatin/pemetrexed improves overall survival (OS). Materials and Methods: Using nationally representative curated electronic health record data from Flatiron Health, we performed a retrospective cohort study of patients diagnosed with advanced nonsquamous NSCLC who received ≥1 cycle of carboplatin/pemetrexed ± bevacizumab as initial systemic therapy for stage IV or metastatic/recurrent disease. The OS impact of adding bevacizumab to carboplatin/pemetrexed was assessed using a Cox proportional hazards model to adjust for age, sex, race, original tumor stage, time between diagnosis of metastatic disease and start of chemotherapy, and performance status. In a secondary analysis of patients at a single academic institution, we also adjusted for the presence of brain metastases, hemoptysis, and anticoagulation. Results: A total of 4,724 patients were included, of which 2,759 patients (58%) received carboplatin/pemetrexed and 1,965 (42%) received carboplatin/pemetrexed/bevacizumab. Median OS was 12.1 months (95% CI, 11.2–12.9 months) in the carboplatin/pemetrexed/bevacizumab group compared with 8.6 months (95% CI, 8.1–9.1 months) in the carboplatin/pemetrexed group (P<.001). Bevacizumab use remained associated with improved OS in a multivariate model (hazard ratio, 0.80; 95% CI, 0.75–0.86; P<.001). In the secondary, institutional analysis (N=539), the effect of bevacizumab was unchanged (hazard ratio, 0.75; 95% CI, 0.59–0.96; P=.02). Conclusions: In this large, real-world dataset, the addition of bevacizumab to first-line carboplatin/pemetrexed for metastatic nonsquamous NSCLC was associated with improved OS.

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Brandon R. Mason, James A. Eastham, Brian J. Davis, Lance A. Mynderse, Thomas J. Pugh, Richard J. Lee and Joseph E. Ippolito

Prostate cancer (PCa) represents a significant source of morbidity and mortality for men in the United States, with approximately 1 in 9 being diagnosed with PCa in their lifetime. The role of imaging in the evaluation of men with PCa has evolved and currently plays a central role in diagnosis, treatment planning, and evaluation of recurrence. Appropriate use of multiparametric MRI (mpMRI) and MRI-guided transrectal ultrasound (MR-TRUS) biopsy increases the detection of clinically significant PCa while decreasing the detection of clinically insignificant PCa. This process may help patients with clinically insignificant PCa avoid the adverse effects of unnecessary therapy. In the setting of a known PCa, patients with low-grade disease can be observed using active surveillance, which often includes a combination of prostate-specific antigen (PSA) testing, serial mpMRI, and, if indicated, follow-up systematic and targeted TRUS-guided tissue sampling. mpMRI can provide important information in the posttreatment setting, but PET/CT is creating a paradigm shift in imaging standards for patients with locally recurrent and metastatic PCa. This article examines the strengths and limitations of mpMRI for initial PCa diagnosis, active surveillance, recurrent disease evaluation, and image-guided biopsies, and the use of PET/CT imaging in men with recurrent PCa. The goal of this review is to provide a rational basis for current NCCN Clinical Practice Guidelines in Oncology for PCa as they pertain to the use of these advanced imaging modalities.

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Suzanne George

The past year has led to significant changes in systemic therapies used to treat soft tissue sarcomas, mainly dominated by the removal of the recently approved drug olaratumab as part of combination therapy with doxorubicin from the NCCN Guidelines for Soft Tissue Sarcoma, according to Dr. Suzanne George. Several histology-specific drugs have entered the space, including pazopanib and pembrolizumab, the latter of which was approved as a category 2B recommendation for alveolar soft part sarcoma, highlighting the rather limited role of immunotherapy in sarcomas. Dr. George also discussed updated data for sorafenib in the treatment of desmoid tumors, as well as the importance of larotrectinib in TRK fusion–positive tumors.

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Margaret Tempero

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Heather H. Cheng, Alexandra O. Sokolova, Edward M. Schaeffer, Eric J. Small and Celestia S. Higano

It is increasingly important for clinicians involved in the management of prostate cancer to understand the relevance of heritable (germline) mutations that, for select patients, affect prostate cancer risk and cancer biology, and acquired (somatic) mutations that occur in prostate cancer cells. In the advanced disease setting, mutations in homologous recombination repair genes (eg, BRCA1, BRCA2, ATM, CHEK2, PALB2) suggest candidacy for platinum chemotherapy and PARP inhibitor trials. Similarly, microsatellite instability and mismatch repair deficiency, which may arise in the setting of MLH1, MSH2, MSH6, and PMS2 mutations, suggest potential vulnerability to PD-1 inhibitors. Germline genetic testing has potential importance in the treatment and assessment of familial risk, and tumor-directed somatic sequencing may guide treatment decision-making. This review provides clinicians with knowledge of basic genetic terminology, awareness of the importance of family history of cancer (not limited to prostate cancer), contrasts between the different but potentially related objectives of germline versus somatic testing of tumor tissue, and indications for genetic counseling. Specific clinical scenarios, objectives of testing, and nature of the assays are reviewed. Germline and somatic mutations of known and potential relevance to prostate cancer are discussed in the context of treatment options, and algorithms to assist clinicians in approaching this area are proposed.

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Linda Overholser and Carlin Callaway

Most cancer survivors will follow-up with primary care at some point in the cancer continuum, but coordination between the oncology and primary care teams remains challenging. According to Drs. Linda Overholser and Carlin Callaway, who discussed the importance of care coordination to improve outcomes in cancer survivors at the NCCN 2019 Annual Conference, effective communication is needed between specialists and primary care providers and, when established, has been shown to improve treatment outcomes. Use of survivorship care plans, as well as adherence to the NCCN Guidelines for Survivorship, can further standardize the provision of quality oncology care.

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U-Syn Ha, Jin Bong Choi, Jung Im Shim, Minjoo Kang, Eunjung Park, Shinhee Kang, Jooyeon Park, Jangmi Yang, Insun Choi, Jeonghoon Ahn, Cheol Kwak, Chang Wook Jeong, Choung Soo Kim, Seok-Soo Byun, Seong Il Seo, Hyun Moo Lee, Seung-Ju Lee, Seung Hwan Lee, Byung Ha Chung and Ji Youl Lee

Background: We conducted a comparative survival analysis between primary androgen deprivation therapy (PADT) and radical prostatectomy (RP) based on nationwide Korean population data that included all patients with prostate cancer. Materials and Methods: This study enrolled 4,538 patients with prostate cancer from the National Health Insurance Service (NHIS) database linked with Korean Central Cancer Registry data who were treated with PADT or RP between January 1, 2007, and December 31, 2014. Kaplan-Meier and multivariate survival analyses stratified by stage (localized and locally advanced) and age (<75 and ≥75 years) were performed using a Cox proportional hazards model to evaluate treatment effects. Results: Among 18,403 patients from the NHIS database diagnosed with prostate cancer during the study period, 4,538 satisfied inclusion criteria and were included in the analyses. Of these, 3,136 and 1,402 patients underwent RP or received PADT, respectively. Risk of death was significantly increased for patients who received PADT compared with those who underwent RP in the propensity score–matched cohort. In subgroup analyses stratified by stage and age, in every subgroup, patients who received PADT had a significantly increased risk of death compared with those who underwent RP. In particular, a much greater risk was observed for patients with locally advanced prostate cancer. Conclusions: Based on a nationwide survival analysis of nonmetastatic prostate cancer, this study provides valuable clinical implications that favor RP over PDAT for treatment of Asian populations. However, the possibility that survival differences have been overestimated due to not accounting for potential confounding characteristics must be considered.